Coexpression of Alternatively Spliced Estrogen and Progesterone Receptor Transcripts in Human Breast Cancer1
Rosemary L. Balleine2,
Sybille M. N. Hunt and
Christine L. Clarke
Westmead Institute for Cancer Research, University of Sydney,
Westmead Hospital, Westmead, New South Wales 2145, Australia
Address all correspondence and requests for reprints to: Dr. Rosemary Balleine, Westmead Institute for Cancer Research, University of Sydney, Westmead Hospital, Westmead, New South Wales 2145, Australia. E-mail: rosemary{at}hemonc.wh.su.edu.au
Primary transcripts of the human estrogen receptor (ER) and
progesteronereceptor (PR) are subject to a number of alternative
splicingevents resulting in a range of variant messenger ribonucleic
acidspecies in receptor-positive tissues. Despite in
vitro demonstrationsof a possible role for some of these
variants in hormonal sensitivity,the clinical significance of this
process is uncertain. In thisstudy the coexpression of variant ER and
PR transcripts hasbeen documented by RT-PCR and Southern blot analysis
in a seriesof receptor-positive breast tumors. In 35 ER-positive
tumors,a common profile of variant ER transcripts was present, with
alltumors containing the 2ER and 7ER,
94% containing the 4ER, and83% containing the
5ER. In 25 of these cases, which were alsoPR positive,
the most highly expressed PR variants, the 4PR,
6PR,and 4/2PR, a transcript from which a
126-bp portion of PR exon4 was deleted, were detected in over 90% of
the cases. The alternativelyspliced ER variants were expressed at
higher relative levelsthan the PR species, which had mean levels of
expression lessthan 10% that of wild-type PR. The most abundant
species wasthe 7ER, which was present at levels ranging
from 29–83%of the wild type. There was no relationship between the
levelof 7ER in individual tumors and the pattern of
expression ofthe estrogen-responsive proteins PR and pS2. The common
profileof alternatively spliced ER and PR transcripts in breast tumors
meansthat this feature cannot be used as a discriminator of hormone
responsivenessor other clinical end points. Further, the low level of
expressionof the majority of variant species calls into question their
potentialfor impacting significantly on receptor function.
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2ER and 
